Vitamin D Deficiency Attenuates High-Fat Diet-Induced Hyperinsulinemia and Hepatic Lipid Accumulation in Male Mice

Liu, Xiaojing; Wang, Bi-Wei; Zhang, Cheng; Xia, Mi-Zhen; Chen, Yuan-Hua; Hu, Chunqiu; Wang, Hua; Chen, Xi; D, Xu

doi:10.1210/en.2014-2037

Cited by 44 publications

(42 citation statements)

References 55 publications

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“…Overall, our findings that vitamin D insufficiency had no effect on BMI in our mice run contrary to findings by Bastie et al [14] and to a lesser extent Liu et al [13], where diet induced vitamin D deficient mice were resistant to “western” and high fat diet induced weight gain, respectfully. However these studies induced vitamin D deficiency concurrently with alterations in diet.…”

Section: Resultscontrasting

confidence: 99%

“…Contrary to what is seen in human trials, animal studies appear to show that vitamin D may promote weight gain. Vitamin D receptor (VDR) knock-out mice were shown to be resistant to weight gain [11, 12], as were diet-induced vitamin D deficient/insufficient mice to high fat [13] and “western” diets [14]. Additionally, over-expression of VDR in adipocytes induced weight gain in mice [15].…”

Section: Introductionmentioning

confidence: 99%

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A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity?

et al. 2017

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BackgroundVitamin D insufficiency (serum 25-OH vitamin D > 10 ng/ml and < 30 ng/ml) is prevalent in the obese (body mass index (BMI) > 30 kg/m2), yet relationships between the two are poorly understood. Objectives of this study include identification of the impact of obesity on reducing serum 25-OH vitamin D concentration, particularly in response to altered vitamin D3 supplementation, and to elucidate the longitudinal impact of serum 25-OH vitamin D on body mass index.MethodsTwenty four-week-old lean and obese male C57BL/6 J mice were fed low, standard, or high levels of cholecalciferol supplementation and followed for 24 weeks. Longitudinal measurements include serum 25-OH and 1,25-(OH)2 vitamin D, intact PTH, and calcium concentrations, as well as BMI, bone density and body fat/lean mass.ResultsBaseline serum 25-OH concentrations were not different in lean and obese mice (lean 32.8 ± 4.4 ng/ml versus obese 30.9 ± 1.6 ng/ml p = 0.09). Lean mice receiving low supplementation exhibited rapid declines in serum 25-OH vitamin D concentrations, falling from 33.4 ± 5.4 ng/ml to 14.5 ± 3.4 ng/ml after 2 weeks, while obese mice declined at a lower rate, falling from 30.9 ± 1.5 to 19.0 ± 0.9 ng/ml within the same time period. Surprisingly, high vitamin D3 supplementation did not substantially increase serum vitamin D concentrations above standard supplementation, in either lean or obese mice. No differences in serum 1,25-(OH)2 vitamin D, intact parathyroid hormone (PTH) or serum calcium were observed between lean and obese mice within the same vitamin D supplementation group. Yet obese mice exhibited lower serum calcitriol, higher serum PTH, and lower bone mineral density (BMD) than did lean mice. Additionally, neither body mass index nor body fat % was significantly correlated with vitamin D concentrations. Interestingly, lean mice with high vitamin D supplementation consumed significantly more food than did lean mice with standard or low supplementation (14.6 ± 1.7 kcal/mouse/day versus 11.8 ± 1.4 and 12.3 ± 1.7 respectively, p < 0.0001 for both).ConclusionsLow cholecalciferol supplementation in both lean and obese mice significantly and sustainably reduces serum 25-OH vitamin D concentrations. Interestingly, obesity slowed the rate of decline. Over the period of the study, vitamin D insufficiency was not subsequently correlated with greater BMI/body fat, although lean mice with high supplementation consumed greater calories with no apparent BMI increase.

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Section: Resultscontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity?

et al. 2017

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“…These VDR null mice fed a high-fat diet displayed reduced lipid accumulation in the liver through greater fatty acid oxidation and increased expression of uncoupling proteins (UCPs), UCP-1, UCP-2, which increases energy expenditure [46]. Dietary induced vitamin D deficiency also alleviates hepatic lipid accumulation, upregulates key enzymes involved in fatty acid oxidation and uncoupling protein 3 (UCP-3) [47]. UCP-1 is an important regulator of proton flux, and can allow dissipation of the proton gradient across the mitochondrial inner membrane in specialised tissues such as brown adipose tissue [46].…”

Section: Discussionmentioning

confidence: 99%

Prevailing vitamin D status influences mitochondrial and glycolytic bioenergetics in peripheral blood mononuclear cells obtained from adults

et al. 2016

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BackgroundCirculating peripheral blood mononuclear cells (PBMCs) are exposed to metabolic and immunological stimuli that influence their functionality. We hypothesized that prevailing vitamin D status [25(OH)D] would modulate the bioenergetic profile of PBMCs derived from humans.Materials and methods38 participants (16 males, 22 females) ranging in body fat from 14–51% were studied. PBMCs were isolated from whole blood, counted and freshly seeded for bioenergetic analysis using the Seahorse XFe96 flux analyser. Whole body energy metabolism via indirect calorimetry, body composition by dual-energy X-ray absorptiometry, and relevant clinical biochemistry were measured. Data was analysed based on 25(OH)D cut-offs of <50 nmol/L (Group 1, n=12), 50–75 nmol/L (Group 2, n=15) and ≥75 nmol/L (Group 3, n=11). A multivariate general linear model adjusting for age, fat mass, fat-free mass, parathyroid hormone and insulin sensitivity was used.ResultsThere were significant differences in cellular mitochondrial function between groups. Group 1 had significantly higher basal respiration (p=0.001), non-mitochondrial respiration (p=0.009), ATP production (p=0.001), proton leak (p=0.018), background glycolysis (p=0.023) and glycolytic reserve (p=0.039) relative to either Group 2 or Group 3; the latter two did not differ on any measures. There were no differences in bioenergetic health index (BHI), resting metabolic rates and systemic inflammatory markers between groups.ConclusionsInadequate vitamin D status adversely influenced bioenergetic parameters of PBMCs obtained from adults, in a pattern consistent with increased oxidative metabolism and activation of these cells.

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“…Moreover, several studies have also report that low serum 1,25(OH) 2 D 3 levels are associated with a higher body mass index (BMI) and body fat mass in healthy adults (Kayaniyil et al, ; Parikh et al, ). However, our previous study also shows that vitamin D deficiency alleviates high‐fat diet‐induced overweight, hyperinsulinemia, and hepatic lipid accumulation in male mice (Liu et al, ). Thus, it is especially interesting to further explore the effects of vitamin D deficiency on acute alcohol‐induced hepatic lipid accumulation in mice.…”

Section: Introductionmentioning

confidence: 93%

Vitamin D Deficiency Attenuates Acute Alcohol‐Induced Hepatic Lipid Accumulation in Mice

Yang

et al. 2019

Lipids

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Vitamin D deficiency has been frequently reported in chronic liver disease. However, its influence on hepatic lipid accumulation in alcoholic liver disease remains unclear. The present study investigated the effects of vitamin D deficiency on acute alcohol‐induced hepatic lipid metabolism in mice. Mice were fed with vitamin D deficient diet, in which vitamin D was depleted for 12 weeks to establish an animal model of vitamin D deficiency. Some mice were administered a single gavage of alcohol (4 g/kg bodyweight) before they were euthanized. Results show that feeding mice with vitamin D deficient diet did not induce hepatic lipid accumulation. In contrast, vitamin D deficiency markedly reduced alcohol‐induced triacylglycerol (TAG) content and prevented hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated alcohol‐induced sterol‐regulated element‐binding protein (SREBP)‐1c activation, which regulates genes for hepatic fatty acid (FA) and TAG synthesis, and the expression of its target genes fatty acid synthase (Fasn) and acetyl‐coenzyme‐ A carboxylase (Acc). In addition, vitamin D deficiency alleviated alcohol‐induced downregulation of hepatic nuclear peroxisome proliferator‐activated receptor (PPAR)α, which governs FA transport and β‐oxidation, and the expression of Carnitine palmitoyltransferase (Cpt)‐1α, cytochrome P450, family 4, subfamily a, polypeptide (Cyp4a)10, and Cyp4a14, which are key enzymes for hepatic fatty acids β‐oxidation and ω‐oxidation. Taken together, these results suggest that vitamin D deficiency is not a direct risk factor for hepatic lipid accumulation. Vitamin D deficiency alleviates acute alcohol‐induced hepatic lipid accumulation through inhibiting hepatic de novo fatty acid syntheses and promoting fatty acid β‐oxidation and ω‐oxidation.

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Vitamin D Deficiency Attenuates High-Fat Diet-Induced Hyperinsulinemia and Hepatic Lipid Accumulation in Male Mice

Cited by 44 publications

References 55 publications

A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity?

A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity?

Prevailing vitamin D status influences mitochondrial and glycolytic bioenergetics in peripheral blood mononuclear cells obtained from adults

Vitamin D Deficiency Attenuates Acute Alcohol‐Induced Hepatic Lipid Accumulation in Mice

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